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1.
J Marital Fam Ther ; 50(2): 495-507, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38356121

RESUMO

The aims of the current study are to describe the basic family relationships, parental bonding patterns, and dyadic adjustment of families with offspring diagnosed with borderline personality disorder (BPD) and to explore the correlations between these variables related to family relations and BPD symptomatology. The sample consisted of 194 participants, including parents from the control (N = 76) and clinical group (N = 76), and patients with BPD (N = 42). All progenitors completed a measure of family relations, parental bonding, and dyadic adjustment. Patients completed a measure of parental bonding and borderline symptomatology. The results showed significant differences between both groups in marital and parental functioning, marital satisfaction, dyadic adjustment, and care. Correlations among family variables and BPD symptomatology were also found. In summary, findings underscore the significance of comprehending the complexity of family relationships in BPD while advocating for a relational perspective when examining the family dynamics.


Assuntos
Transtorno da Personalidade Borderline , Humanos , Transtorno da Personalidade Borderline/diagnóstico , Relações Familiares , Pais , Apego ao Objeto
2.
Int J Pharm ; 652: 123855, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38280497

RESUMO

Tioconazole is an effective antifungal agent with very low solubility in aqueous media, which limits its bioavailability and efficacy. Aiming to overcome the drug limitations by improving the solubility of this active pharmaceutical ingredient, solution precipitation techniques were employed to prepare four new crystalline salts, namely the mesylate, tosylate, maleate (1:1), and fumarate (1:1) hemihydrate. The thermal stabilities, dissolution properties, and structural characteristics of the solids were determined, and the study was extended to compare their properties with the already-known oxalate salt. The structural characterization of the new phases was carried out using a multi-method approach, which included thermal (differential scanning calorimetry and thermogravimetry), diffractometric (powder X-ray diffraction), and spectroscopic (near-infrared and mid-infrared) methodologies. The determination of the melting point of the salts confirmed the findings made by thermal methods. Functional characteristics of the salts, involving their intrinsic dissolution rates were also determined. It was found that the salts exhibited improved thermal stability and that the nature of the counterion modulated their dissolution characteristics. The salts displayed better intrinsic dissolution rates than the free base, to the point of being "highly soluble" according to the Biopharmaceutical Classification System. At pH 4.3, the sulfonic acid derivatives exhibited better dissolution rates than their carboxylic acid-derived counterparts, greatly improved regarding bare tioconazole. The results suggest that the salts have great potential to be used as replacements for the free base; in principle, careful salt selection may help to fulfill each solubility need for the different scenarios where the drug may be used.


Assuntos
Imidazóis , Sais , Sais/química , Difração de Raios X , Oxalatos , Solubilidade , Varredura Diferencial de Calorimetria
3.
Neuropsychobiology ; 83(1): 49-60, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38253028

RESUMO

INTRODUCTION: Recall of autobiographical events has been found to be impaired in borderline personality disorder (BPD), but few studies have examined if this impairment has brain functional correlates. This study evaluated brain functional alterations during autobiographical recall using medication-naive adolescent patients to avoid potential confounding effects of treatment. METHODS: Thirty-two adolescent female patients with BPD who were never-medicated and without psychiatric comorbidity and 33 matched healthy females underwent fMRI while they viewed individualized cue words that evoked autobiographical memories. Control conditions included viewing non-memory-evoking cues and a low-level baseline (cross-fixation). RESULTS: During autobiographical recall, in comparison to the low-level baseline, the BPD patients showed increased brain activity in regions including the posterior hippocampus, the lingual and calcarine cortex, and the precuneus compared to the healthy controls. The BPD patients also showed a failure to deactivate the right dorsolateral prefrontal cortex during autobiographical recall. No patient-control differences were found when memory-evoking words were compared to non-memory-evoking words. DISCUSSION/CONCLUSIONS: This study finds evidence of hippocampal/lingual/calcarine/precuneus hyperactivation to stimuli that evoke autobiographical memories in patients with BPD. As the changes were seen in never-treated patients without other comorbidities, they could be considered intrinsic to the disorder. Our study also adds to existing evidence for failure of deactivation in BPD, this time outside the default mode network.


Assuntos
Transtorno da Personalidade Borderline , Humanos , Feminino , Adolescente , Encéfalo/diagnóstico por imagem , Rememoração Mental/fisiologia , Mapeamento Encefálico , Imageamento por Ressonância Magnética
4.
Dalton Trans ; 53(2): 808-819, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38087997

RESUMO

Two novel Cu(I) tetradentate heteroleptic complexes, including nitrile-substituted bipyridines that can be anchored to semiconductor surfaces to be assembled in DSSCs, were synthesized and characterized by spectroscopic and electrochemical techniques. The crystal structures of both species were determined by X-ray diffraction. Results from DFT and TD-DFT calculations were found to be consistent with the experimental data. Emission at room temperature was observed for both complexes in the solid state, making them promising alternatives for the development of light-emitting diodes. We report for the first time the experimental evidence of photovoltaic conversion devices formed by Cu(I) complexes anchored to a TiO2 surface by means of nitrile groups present in substituted bipyridines, and subsequently tested as sensitizers for DSSCs, obtaining efficiency values for light to electrical energy conversion similar to those previously reported for analogous complexes with anchoring carboxylic groups.

5.
Heliyon ; 9(6): e17381, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37416660

RESUMO

Dilocarcinus pagei is a South American crab commonly found in fishponds. As crabs are a source of astaxanthin (AST) and food inputs, this preliminary research aimed at studying the composition of females and males of this species to assess its potential for commercial applications, and at optimising the extraction of AST with edible oils to promote its use as an ingredient for the nutraceutical, pharmaceutical and feed industries. The chemical composition differed between males and females only in moisture, and the values obtained were: 65.4 ± 1.0% and 72.5 ± 3.1% moisture, 45.7-40.3% d.m. minerals, 22.0-24.1% d.m. fibres, 18.2-17.4% d.m. proteins, and 10.4-11.1% d.m. lipids. The Box-Behnken design was applied and validated for extraction with soya bean and sunflower oils, adjusting the oil:crab ratio, temperature, and extraction time. The optimal conditions found consisted of 140 mL/g, 90 °C and 170 min for soya bean oil, reaching an accumulation of AST of 50 ± 5 µg/g crab d.m. For sunflower oil, the conditions were 60 mL/g, 90 °C and 161 min, reaching 31 ± 3 µg/g crab d.m. Finally, the amounts of AST obtained using soya bean oil were higher than those obtained using sunflower oil; thus, soya bean oil would be recommended as a solvent to extract the pigment.

6.
Eur Neuropsychopharmacol ; 74: 47-63, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37276836

RESUMO

Several studies performed on human subjects have examined the effects of adolescent cannabis consumption on brain structure or function using brain imaging techniques. However, the evidence from these studies is usually heterogenous and affected by several confounding variables. Animal models of adolescent cannabinoid exposure may help to overcome these difficulties. In this exploratory study, we aim to increase our understanding of the protracted effects of adolescent Δ9-tetrahydrocannabinol (THC) in rats of both sexes using magnetic resonance (MR) to obtain volumetric data, assess grey and white matter microstructure with diffusion tensor imaging (DTI) and measure brain metabolites with 1H-MR spectroscopy (MRS); in addition, we studied brain function using positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-glucose as the tracer. THC-exposed rats exhibited volumetric and microstructural alterations in the striatum, globus pallidus, lateral ventricles, thalamus, and septal nuclei in a sex-specific manner. THC administration also reduced fractional anisotropy in several white matter tracts, prominently in rostral sections, while in vivo MRS identified lower levels of cortical choline compounds. THC-treated males had increased metabolism in the cerebellum and olfactory bulb and decreased metabolism in the cingulate cortex. By contrast, THC-treated females showed hypermetabolism in a cluster of voxels comprising the entorhinal piriform cortices and in the cingulate cortex. These results indicate that mild THC exposure during adolescence leaves a lingering mark on brain structure and function in a sex-dependant manner. Some of the changes found here resemble those observed in human studies and highlight the importance of studying sex-specific effects in cannabinoid research.


Assuntos
Canabinoides , Dronabinol , Ratos , Animais , Masculino , Humanos , Feminino , Adolescente , Dronabinol/farmacologia , Dronabinol/metabolismo , Ratos Wistar , Imagem de Tensor de Difusão , Encéfalo , Canabinoides/farmacologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-37189168

RESUMO

BACKGROUND: Although the diagnosis of Borderline Personality Disorder (BPD) during adolescence has been questioned, many recent studies have confirmed its validity. However, some clinical manifestations of BPD could be identifiable in adolescents with other pathologies, such as Attention-Deficit/Hyperactivity Disorder (ADHD). The objective of the present study is to examine the capacity of the self-report Borderline Personality Features Scale Children-11 (BPFSC-11) to discriminate between BPD and ADHD adolescents. METHODS: One hundred and forty-five participants were grouped based on their diagnosis: 58 with BPD, 58 with ADHD, and 29 healthy volunteers as a control group. Between-group differences and the ROC curve were performed to test if the total score for the BPFSC-11 and/or its factors can significantly discriminate between BPD and other adolescent groups. RESULTS: The results show that the total BPFSC-11 score has good discriminant capacity among adolescents diagnosed with BPD, ADHD and healthy volunteers. However, different patterns of discriminative capacity were observed between the three groups for emotional dysregulation and impulsivity/recklessness factors. CONCLUSIONS: Our results support the hypothesis that the BPFSC-11 is an adequate instrument for discriminating between BPD and ADHD in adolescents, who can present significant psychopathological overlap. Tools to identify BPD in adolescence, as well as for better differential diagnosis, would improve the possibility of offering specific treatments targeting these populations.

8.
Materials (Basel) ; 16(9)2023 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-37176470

RESUMO

Oral candidiasis is an opportunistic infection that affects mainly individuals with weakened immune system. Devices used in the oral area to treat this condition include buccal films, which present advantages over both oral tablets and gels. Since candidiasis causes pain, burning, and itching, the purpose of this work was to develop buccal films loaded with both lidocaine (anesthetic) and miconazole nitrate (MN, antifungal) to treat this pathology topically. MN was loaded in microparticles based on different natural polymers, and then, these microparticles were loaded in hydroxypropyl methylcellulose-gelatin-based films containing lidocaine. All developed films showed adequate adhesiveness and thickness. DSC and XRD tests suggested that the drugs were in an amorphous state in the therapeutic systems. Microparticles based on chitosan-alginate showed the highest MN encapsulation. Among the films, those containing the mentioned microparticles presented the highest tensile strength and the lowest elongation at break, possibly due to the strong interactions between both polymers. These films allowed a fast release of lidocaine and a controlled release of MN. Due to the latter, these systems showed antifungal activity for 24 h. Therefore, the treatment of oropharyngeal candidiasis with these films could reduce the number of daily applications with respect to conventional treatments.

9.
Transl Psychiatry ; 13(1): 84, 2023 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-36890154

RESUMO

Substance use disorders are more prevalent in schizophrenia, but the causal links between both conditions remain unclear. Maternal immune activation (MIA) is associated with schizophrenia which may be triggered by stressful experiences during adolescence. Therefore, we used a double-hit rat model, combining MIA and peripubertal stress (PUS), to study cocaine addiction and the underlying neurobehavioural alterations. We injected lipopolysaccharide or saline on gestational days 15 and 16 to Sprague-Dawley dams. Their male offspring underwent five episodes of unpredictable stress every other day from postnatal day 28 to 38. When animals reached adulthood, we studied cocaine addiction-like behaviour, impulsivity, Pavlovian and instrumental conditioning, and several aspects of brain structure and function by MRI, PET and RNAseq. MIA facilitated the acquisition of cocaine self-administration and increased the motivation for the drug; however, PUS reduced cocaine intake, an effect that was reversed in MIA + PUS rats. We found concomitant brain alterations: MIA + PUS altered the structure and function of the dorsal striatum, increasing its volume and interfering with glutamatergic dynamics (PUS decreased the levels of NAA + NAAG but only in LPS animals) and modulated specific genes that could account for the restoration of cocaine intake such as the pentraxin family. On its own, PUS reduced hippocampal volume and hyperactivated the dorsal subiculum, also having a profound effect on the dorsal striatal transcriptome. However, these effects were obliterated when PUS occurred in animals with MIA experience. Our results describe an unprecedented interplay between MIA and stress on neurodevelopment and the susceptibility to cocaine addiction.


Assuntos
Transtornos Relacionados ao Uso de Cocaína , Cocaína , Efeitos Tardios da Exposição Pré-Natal , Ratos , Animais , Masculino , Feminino , Humanos , Transtornos Relacionados ao Uso de Cocaína/complicações , Ratos Sprague-Dawley , Transcriptoma , Encéfalo/diagnóstico por imagem , Cocaína/farmacologia , Modelos Animais de Doenças , Comportamento Animal
10.
J Psychiatr Res ; 161: 40-47, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36898325

RESUMO

BACKGROUND: Patients with borderline personality disorder (BPD) have been found to show functional brain abnormality, including in the medial frontal cortex and other areas of the default mode network (DMN). The current study aimed to examine activations and de-activations in drug treated and medication-free female adolescents with the disorder. METHODS: 39 DSM-5 adolescent female patients with BPD without psychiatric comorbidity and 31 matched healthy female adolescents underwent fMRI during the performance of 1-back and 2-back versions of the n-back working memory task. Linear models were used to obtain maps of within-group activations and de-activations and areas of differences between the groups. RESULTS: On corrected whole-brain analysis, the BPD patients showed failure to de-activate a region of the medial frontal cortex in the 2-back > 1-back comparison. The 30 never-medicated patients additionally showed a failure to de-activate the right hippocampus in the 2-back versus baseline contrast. CONCLUSIONS: Evidence of DMN dysfunction was observed in adolescent patients with BPD. Because the relevant medial frontal and hippocampal changes were seen in unmedicated young patients without comorbidity, they might be considered intrinsic to the disorder.


Assuntos
Transtorno da Personalidade Borderline , Humanos , Feminino , Adolescente , Rede de Modo Padrão , Encéfalo/diagnóstico por imagem , Lobo Frontal/diagnóstico por imagem , Memória de Curto Prazo/fisiologia , Imageamento por Ressonância Magnética , Mapeamento Encefálico
11.
Int J Pharm ; 637: 122869, 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-36948477

RESUMO

Tioconazole is an effective antifungal agent, which has a very low solubility in aqueous media, that limits its bioavailability and efficacy. In an effort to overcome the drug limitations by improving its solubility, the hydrochloride salt was prepared in methanolic 1 M HCl and obtained as the hemihydrate, as demonstrated by elemental analysis. Single crystals were grown by slow evaporation from an aqueous 1 M HCl solution and their structure was determined using single-crystal X-ray diffraction at 302 K. The structures resulting from dehydration and further rehydration were also assessed, at 333 and 283 K, respectively. The morphology of the crystal, which exhibited birefringence under polarized light, was verified by hot stage microscopy. The solid was characterized by additional means, including thermal analysis (melting point, differential scanning calorimetry and thermogravimetry), spectroscopic methods (mid infrared, near infrared, 1H, 13C and 15N nuclear magnetic resonance in solution, as well as 13C and 15N solid state with spinning at the magic angle) and X-ray diffraction techniques. Functional evaluation tests, including the intrinsic dissolution rate and the dissolution of powders were also performed. In the intrinsic dissolution rate test, the salt proved to dissolve over 2000 times faster than tioconazole. The results suggest that the new salt has physicochemical and performance properties which may support its use as a replacement of the free base in certain applications, especially where improved dissolution rate, solubility or bioavailability of the drug would be desired.


Assuntos
Antifúngicos , Cloreto de Sódio , Difração de Raios X , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Varredura Diferencial de Calorimetria , Água/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
12.
J Pharm Sci ; 112(6): 1523-1538, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36822273

RESUMO

Nifurtimox is a nitroheterocyclic drug employed for treatment of trypanosomiases (Chagas disease and West African sleeping sickness); its use for certain cancers has also been assessed. Despite having been in the market for over 50 years, knowledge of nifurtimox is still fragmentary and incomplete. Relevant aspects of the chemistry and biology of nifurtimox are reviewed to summarize the current knowledge of this drug. These comprise its chemical synthesis and the preparation of some analogues, as well as its chemical degradation. Selected physical data and physicochemical properties are also listed, along with different approaches toward the analytical characterization of the drug, including electrochemical (polarography, cyclic voltammetry), spectroscopic (ultraviolet-visible, nuclear magnetic resonance, electron spin resonance), and single crystal X-ray diffractometry. The array of polarographic, ultraviolet-visible spectroscopic, and chromatographic methods available for the analytical determination of nifurtimox (in bulk drug, pharmaceutical formulations, and biological samples), are also presented and discussed, along with chiral chromatographic and electrophoretic alternatives for the separation of the enantiomers of the drug. Aspects of the drug likeliness of nifurtimox, its classification in the Biopharmaceutical Classification System, and available pharmaceutical formulations are detailed, whereas pharmacological, chemical, and biological aspects of its metabolism and disposition are discussed.


Assuntos
Doença de Chagas , Farmácia , Humanos , Nifurtimox/química , Nifurtimox/farmacologia , Nifurtimox/uso terapêutico , Doença de Chagas/tratamento farmacológico , Preparações Farmacêuticas
13.
Eur J Pharm Biopharm ; 184: 25-35, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36681284

RESUMO

Nifurtimox (NFX) is a nitrofuran derivative used to treat Chagas disease, a neglected disease caused by the protozoan Trypanosoma cruzi. The drug is very sparingly soluble in aqueous media and no other solid phases of NFX have been reported to date. The preparation of the amorphous mode of NFX is reported, as well as its characterization by hot stage microscopy, thermal (differential scanning calorimetry and thermogravimetric analysis), spectroscopic (solid state nuclear magnetic resonance, mid-infrared, and near-infrared), diffractometric and functional (powder dissolution rate) means. The stability of the new phase was investigated. This was characterized using thermal, spectroscopic, and diffractometric methods, finding out its spontaneous reversion to the crystalline state, as sign of instability. In addition, the amorphous material proved to be sensitive to temperature, pressure, and mechanical stress, all of which accelerated phase conversion. However, it was able to remain stable in a model polymeric amorphous solid dispersion with PEG 4000 for more than one month. An approach for monitoring the conversion of the amorphous phase to its crystalline counterpart under thermal stress by chemometric analysis of mid-infrared spectra at different temperatures is also disclosed.


Assuntos
Nifurtimox , Estabilidade de Medicamentos , Cristalização , Varredura Diferencial de Calorimetria , Temperatura , Solubilidade , Difração de Raios X , Espectroscopia de Infravermelho com Transformada de Fourier
14.
Personal Disord ; 14(3): 355-359, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35737563

RESUMO

The inclusion of the borderline pattern in the International Classification of Diseases, 11th Revision (ICD-11) dimensional classification of personality disorders (PDs) has caused controversy. Unease about leaving out these clinically challenging patients seems to conflict with the need of an evidence-based and credible diagnostic system. However, the accommodation of borderline within the new diagnostic system has not yet been studied in depth. To this end, we examine in a sample of 1799 general population and clinical subjects the joint structure of the five initial ICD-11 domains and the borderline pattern. Regression and item-level factor analyses reveal that borderline criteria do not form a separate construct and are indissociable from negative affectivity. Furthermore, borderline adds nothing to the remaining domains when it comes to predict PD severity. The borderline pattern appears as largely superfluous and even misguiding, unless their criteria are properly integrated within the structure of personality pathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Classificação Internacional de Doenças , Transtornos da Personalidade , Humanos , Psicometria , Inventário de Personalidade , Manual Diagnóstico e Estatístico de Transtornos Mentais , Transtornos da Personalidade/diagnóstico , Personalidade
15.
World J Gastroenterol ; 28(26): 3177-3200, 2022 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-36051345

RESUMO

BACKGROUND: Parathyroid hormone-related peptide (PTHrP) plays a key role in the development and progression of many tumors. We found that in colorectal cancer (CRC) HCT116 cells, the binding of PTHrP to its receptor PTHR type 1 (PTHR1) activates events associated with an aggressive phenotype. In HCT116 cell xenografts, PTHrP modulates the expression of molecular markers linked to tumor progression. Empirical evidence suggests that the Met receptor is involved in the development and evolution of CRC. Based on these data, we hypothesized that the signaling pathway trigged by PTHrP could be involved in the transactivation of Met and consequently in the aggressive behavior of CRC cells. AIM: To elucidate the relationship among PTHR1, PTHrP, and Met in CRC models. METHODS: For in vitro assays, HCT116 and Caco-2 cells derived from human CRC were incubated in the absence or presence of PTHrP (1-34) (10-8 M). Where indicated, cells were pre-incubated with specific kinase inhibitors or dimethylsulfoxide, the vehicle of the inhibitors. The protein levels were evaluated by Western blot technique. Real-time polymerase chain reaction (RT-qPCR) was carried out to determine the changes in gene expression. Wound healing assay and morphological monitoring were performed to evaluate cell migration and changes related to the epithelial-mesenchymal transition (EMT), respectively. The number of viable HCT116 cells was counted by trypan blue dye exclusion test to evaluate the effects of irinotecan (CPT-11), oxaliplatin (OXA), or doxorubicin (DOXO) with or without PTHrP. For in vivo tests, HCT116 cell xenografts on 6-wk-old male N:NIH (S)_nu mice received daily intratumoral injections of PTHrP (40 µg/kg) in 100 µL phosphate-buffered saline (PBS) or the vehicle (PBS) as a control during 20 d. Humanitarian slaughter was carried out and the tumors were removed, weighed, and fixed in a 4% formaldehyde solution for subsequent treatment by immunoassays. To evaluate the expression of molecular markers in human tumor samples, we studied 23 specimens obtained from CRC patients which were treated at the Hospital Interzonal de Graves y Agudos Dr. José Penna (Bahía Blanca, Buenos Aires, Argentina) and the Hospital Provincial de Neuquén (Neuquén, Neuquén, Argentina) from January 1990 to December 2007. Seven cases with normal colorectal tissues were assigned to the control group. Tumor tissue samples and clinical histories of patients were analyzed. Paraffin-embedded blocks from primary tumors were reviewed by hematoxylin-eosin staining technique; subsequently, representative histological samples were selected from each patient. From each paraffin block, tumor sections were stained for immunohistochemical detection. The statistical significance of differences was analyzed using proper statistical analysis. The results were considered statistically significant at P < 0.05. RESULTS: By Western blot analysis and using total Met antibody, we found that PTHrP regulated Met expression in HCT116 cells but not in Caco-2 cells. In HCT116 cells, Met protein levels increased at 30 min (P < 0.01) and at 20 h (P < 0.01) whereas the levels diminished at 3 min (P < 0.05), 10 min (P < 0.01), and 1 h to 5 h (P < 0.01) of PTHrP treatment. Using an active Met antibody, we found that where the protein levels of total Met decreased (3 min, 10 min, and 60 min of PTHrP exposure), the status of phosphorylated/activated Met increased (P < 0.01) at the same time, suggesting that Met undergoes proteasomal degradation after its phosphorylation/activation by PTHrP. The increment of its protein level after these decreases (at 30 min and 20 h) suggests a modulation of Met expression by PTHrP in order to improve Met levels and this idea is supported by our observation that the cytokine increased Met mRNA levels at least at 15 min in HCT116 cells as revealed by RT-qPCR analysis (P < 0.05). We then proceeded to evaluate the signaling pathways that mediate the phosphorylation/ activation of Met induced by PTHrP in HCT116 cells. By Western blot technique, we observed that PP1, a specific inhibitor of the activation of the proto-oncogene protein tyrosine kinase Src, blocked the effect of PTHrP on Met phosphorylation (P < 0.05). Furthermore, the selective inhibition of the ERK 1/2 mitogen-activated protein kinase (ERK 1/2 MAPK) using PD98059 and the p38 MAPK using SB203580 diminished the effect of PTHrP on Met phosphorylation/activation (P < 0.05). Using SU11274, the specific inhibitor of Met activation, and trypan blue dye exclusion test, Western blot, wound healing assay, and morphological analysis with a microscope, we observed the reversal of cell events induced by PTHrP such as cell proliferation (P < 0.05), migration (P < 0.05), and the EMT program (P < 0.01) in HCT116 cells. Also, PTHrP favored the chemoresistance to CPT-11 (P < 0.001), OXA (P < 0.01), and DOXO (P < 0.01) through the Met pathway. Taken together, these findings suggest that Met activated by PTHrP participates in events associated with the aggressive phenotype of CRC cells. By immunohistochemical analysis, we found that PTHrP in HCT116 cell xenografts enhanced the protein expression of Met (0.190 ± 0.014) compared to tumors from control mice (0.110 ± 0.012; P < 0.05) and of its own receptor (2.27 ± 0.20) compared to tumors from control mice (1.98 ± 0.14; P < 0.01). Finally, assuming that the changes in the expression of PTHrP and its receptor are directly correlated, we investigated the expression of both Met and PTHR1 in biopsies of CRC patients by immunohistochemical analysis. Comparing histologically differentiated tumors with respect to those less differentiated, we found that the labeling intensity for Met and PTHR1 increased and diminished in a gradual manner, respectively (P < 0.05). CONCLUSION: PTHrP acts through the Met pathway in CRC cells and regulates Met expression in a CRC animal model. More basic and clinical studies are needed to further evaluate the PTHrP/Met relationship.


Assuntos
Neoplasias Colorretais , Proteína Relacionada ao Hormônio Paratireóideo , Animais , Células CACO-2 , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , Irinotecano , Masculino , Camundongos , Proteína Relacionada ao Hormônio Paratireóideo/genética , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Azul Tripano/farmacologia
17.
J Am Chem Soc ; 144(18): 8185-8193, 2022 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-35486830

RESUMO

We present the synthesis, photophysical properties, and biological application of nontoxic 3-azo-conjugated BODIPY dyes as masked fluorescent biosensors of hypoxia-like conditions. The synthetic methodology is based on an operationally simple N═N bond-forming protocol, followed by a Suzuki coupling, that allows for a direct access to simple and underexplored 3-azo-substituted BODIPY. These dyes can turn on their emission properties under both chemical and biological reductive conditions, including bacterial and human azoreductases, which trigger the azo bond cleavage, leading to fluorescent 3-amino-BODIPY. We have also developed a practical enzymatic protocol, using an immobilized bacterial azoreductase that allows for the evaluation of these azo-based probes and can be used as a model for the less accessible and expensive human reductase NQO1. Quantum mechanical calculations uncover the restructuration of the topography of the S1 potential energy surface following the reduction of the azo moiety and rationalize the fluorescent quenching event through the mapping of an unprecedented pathway. Fluorescent microscopy experiments show that these azos can be used to visualize hypoxia-like conditions within living cells.


Assuntos
Técnicas Biossensoriais , Corantes , Compostos Azo/química , Corantes Fluorescentes/química , Humanos , Hipóxia , Microscopia de Fluorescência
18.
Eur Neuropsychopharmacol ; 58: 86-98, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35325633

RESUMO

Non-suicidal self-injury (NSSI) is a clinically significant behavior with high relevance and prevalence, especially affecting approximately 17-18% of the adolescent population worldwide. The aim of this study is to perform a systematic review to evaluate the effectiveness of the available Specific Psychotherapeutic Interventions (SPI) focused on the reduction of NSSI behaviors. A systematic review was performed analyzing PsychINFO, MEDLINE, Web of Science, PubMed and Cochrane CentralRegister of Controlled Trials to identify studies of interest from January 2010 to December 2020. According to PRISMA guidelines, only 13 studies were included in the review. Six SPI were found to specifically and significantly reduce NSSI in adolescents: Developmental Group Psychotherapy (DGP), Therapeutic Assessment (TA), Cutting Down Program (CDP), Emotional Regulation Individual Therapy for Adolescents (ERITA), Treatment for Self-Injurious Behaviors (T-SIB) and Intensive Contextual Treatment (ICT). Furthermore, relevant improvements in anxiety and depression symptoms were observed. The results of this review demonstrate the effectiveness of these interventions, mainly the CPD and T-SIB, which are the only SPI that have been studied using Randomized Controlled Trial (RCT). Considering the clinical relevance and associated functional impairment of NSSI, more research is needed to replicate the results and to increase knowledge about SPIs.


Assuntos
Comportamento do Adolescente , Regulação Emocional , Comportamento Autodestrutivo , Adolescente , Comportamento do Adolescente/psicologia , Humanos , Psicoterapia/métodos , Psicotrópicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Comportamento Autodestrutivo/diagnóstico , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/terapia
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120354, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34520896

RESUMO

Albendazole is a benzimidazole-type active pharmaceutical ingredient, and one of the most effective broad-spectrum anthelminthic agents. The drug has two solid-state forms (ALB I and ALB II) which are desmotropes; both of them seem to be currently marketed. However, using the wrong crystalline solid form for formulation may have an undesired impact on the physicochemical and/or bioavailability properties of the drug product. In order to develop new, simple, and less expensive alternatives toward the determination of the level of albendazole ALB I in its mixtures with ALB II, both desmotropes were prepared, and properly characterized by spectroscopic [solid-state nuclear magnetic resonance and near infrared (NIR)] and diffractometric (powder X-ray diffraction) methods. Then, the NIR and attenuated total reflectance-mid infrared (ATR-MIR) spectra of both forms were conveniently pre-treated and employed for the development and optimization of partial least squares (PLS)-potentiated quantification models (NIR/PLS and ATR-MIR/PLS). The latter were also subjected to validation (accuracy, precision, limits of detection and quantification, etc.) and further used to assess the level of the unwanted ALB II form in the bulk drug. The NIR/PLS method displayed the most satisfactory characteristics, including a limit of quantitation interval of 3.6 ± 1 %w/w; it outperformed both, the ATR-MIR/PLS counterpart (limit of quantitation interval of 14.0 ± 3.4 %w/w) and a previously published and more demanding Raman/PLS alternative.


Assuntos
Albendazol , Análise dos Mínimos Quadrados , Espectroscopia de Ressonância Magnética , Pós , Difração de Raios X
20.
Clin Child Psychol Psychiatry ; 27(1): 157-176, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34875884

RESUMO

The aim of this study was to explore the impact of the coronavirus pandemic on adolescents diagnosed with Borderline Personality Disorder (BPD) and their mothers. This exploratory study used a qualitative focus group approach. This study's sample group consisted in nine participants: five adolescents diagnosed with BPD and their four mothers. Patients were recruited from a specialized BPD outpatient unit of a university hospital psychiatry department. The results are divided into two main areas, the first regarding the lockdown period and the second examining the period of gradual relaxation of lockdown restrictions. The results show that the adolescents had difficulties in the management of their interpersonal relationships, especially in striking a balance between individual and family space, as well as in communication, cohesion, and family dynamics. During the COVID lockdown, adolescents experienced a stabilization of psychopathological symptoms, but these symptoms worsened when the lockdown restrictions were lifted. Nevertheless, they reported having learned and implemented self-care strategies. The findings are discussed in terms of both individual and family impact, shedding light on some of the challenges precipitated by the COVID-19 pandemic.


Assuntos
Transtorno da Personalidade Borderline , COVID-19 , Adolescente , Controle de Doenças Transmissíveis , Feminino , Grupos Focais , Humanos , Mães , Pandemias , SARS-CoV-2
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